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They’re locked and loaded
COLLEGEVILLE, Pa.—Wyeth Pharmaceuticals announced in mid-January that it entered into a worldwide strategic alliance with Hoersholm, Denmark-based Santaris Pharma to discover, develop and commercialize new medicines based on Santaris Pharma's proprietary Locked Nucleic Acid (LNA) drug platform, which allows specific targeting and regulation of microRNAs (miRNAs) and messenger RNAs (mRNAs) as a means to affect gene expression mediated by the targeted RNAs.
Under the terms of the agreement, Santaris Pharma will receive an upfront payment of $7 million in cash and Wyeth will make a $10 million equity investment in Santaris Pharma. Santaris could also receive further milestone payments of as much as $83 million for each of 10 potential targets on Wyeth's list. In addition, Santaris would receive royalties on the worldwide sales of all products arising from the alliance.
The research portion of the collaboration is for three years, and Wyeth has the right to extend the research portion up to two additional years if it desires.
Wyeth will select the RNA targets against which Santaris Pharma will use its proprietary LNA drug platform to generate unique drug candidates. Wyeth will be responsible for the development and commercialization of products arising from the alliance. Those targets are not being made public, but Wyeth public relations contact Michael Lampe confirms they will all fall into one or more of Wyeth's current areas of discovery research: oncology, vaccines, musculoskeletal disorders, inflammation, metabolic disease or neuroscience.
Although the target of all this work is RNA biology, the LNA platform isn't an RNA interference technology, notes Dr. Robert T. Abraham, vice president of oncology discovery research for Wyeth Pharmaceuticals.
"Essentially, it's a modification of what would be considered a classical antisense strategy. Even though the endpoint is the same—gene silencing—the technology Santaris is using is fundamentally different from RNA interference," Abraham explains. "We liked the partnership with Santaris because it gives us play in a parallel space to RNA interference and with a fundamentally different action. It's not mutually exclusive to RNA interference but complementary, and we're still enthusiastic about using RNA interference as well in our future work."
One reason that going with a more antisense-oriented technology was appealing, Abraham said, was because that even though antisense has been around for some time, it is only recently that some exciting clinical data are emerging from other companies that show, for example, that antisense can yield activity in a solid tumor setting. Whether that means solid tumor targets were among the 10 Wyeth has picked for Santaris, Abraham was not able to confirm.
Another advantage of an antisense approach is that therapies based on such technology could be taken up by cells directly instead of requiring a facilitating reagent, he adds.
"That isn't to say that this technology is superior to RNA interference," Abraham notes, "just that we haven't found an appropriate partner yet for RNA interference, which is why it is nice to have a good partner in this parallel space."
Wyeth Research President Mikael Dolsten has noted this alliance brings forth a fourth platform technology with which to target RNAs, along with the company's existing expertise in platforms involving small molecules, vaccines and protein-based therapeutics. "This will increase our ability to develop and bring to market innovative, high-value medicines that have the potential to address significant unmet needs in critical therapeutic areas," he adds.
The Locked Nucleic Acid-based technology developed by Santaris Pharma creates synthetic chemical versions (LNAs) of the normal nucleic acid building blocks of RNAs. These LNAs improve the drug-like qualities of resulting oligonucleotide therapeutics by increasing resistance to metabolism, increasing half-life and improving tissue uptake. The LNA-based therapeutics also reportedly demonstrate improved binding affinity to their target RNA, which could increase potency many-fold over other nucleotide therapeutics.
"We are delighted to welcome Wyeth as a new major partner," says Soren Tulstrup, president and CEO of Santaris Pharma. "This strategic alliance further consolidates Santaris Pharma's leading position in the rapidly evolving RNA-based therapeutic field. The scope of this collaboration demonstrates the utility of Santaris Pharma's proprietary LNA Drug Platform for developing new therapies targeting RNAs." DDN